© 2008 American Thoracic Society
The INSPIRE Study: Influence of Prior Use and Discontinuation of Inhaled CorticosteroidsFrom the Authors:We thank Drs. Lanes and Jara for their comments on our article (1). They raise important questions regarding the impact on withdrawal, exacerbation, and mortality rates caused by cessation of inhaled corticosteroids (ICS) for those subjects previously treated with ICS and randomized to the tiotropium arm. To support their argument, they refer to an observational study (2), which reported deterioration following steroid withdrawal. This is further evidenced by the 1-year COSMIC study (3). In both studies, ICS discontinuation caused rapid deterioration; however, neither identified different patient withdrawal rates during the course of the study. The differential withdrawal rate between treatment groups in INSPIRE was not apparent until Week 13 and continued to increase for up to a year. This is not consistent with the acute deterioration identified by Jarad and coworkers (2) and by Wouters and coworkers (3) after steroid cessation. Drs. Lanes and Jara further suggest that we should conduct additional analyses of exacerbation and mortality rates based on prior use of ICS. Contrary to their assumption, exacerbation rates were similar between treatment arms in patients according to prior use of ICS. As in our original analyses, the observed on-treatment mortality in the tiotropium arm was approximately double that for salmeterol/fluticasone propionate (SFC) regardless of prior use of ICS. The pattern for all mortality (including patients who had withdrawn from the study, but for whom mortality was known) was similar (see Table 1).
We therefore maintain our original conclusion: in INSPIRE, the withdrawal rate was a measure of efficacy, and more subjects withdrew on tiotropium compared with those on SFC. The additional analyses requested by Drs. Lanes and Jara demonstrate that the survival benefit for patients on SFC was unaffected by prior use of ICS.
Royal Free and University College Medical School
University Hospital Aintree
The University of the West Indies
GlaxoSmithKline
University Hospital Birmingham On behalf of the INSPIRE Investigators FOOTNOTES Conflict of Interest Statement: In the past 3 years, J.A.W. has received research funding from GlaxoSmithKline (GSK), Boehringer Ingelheim, and AstraZeneca; she has received honoraria for lectures and/or attendance at advisory boards from GSK, Boehringer Ingelheim, AstraZeneca, and Novartis. P.M.A.C. has received honoraria for serving on study advisory boards for GSK and Pfizer, and has received funding to conduct clinical trials by GSK, Altana, and Chiesi. T.A.S. has been sponsored to attend several conferences by AstraZeneca and GSK in the past 3 years. G.H. was an employee of GSK between 1996 and 2008 and as such holds a number of stock options in various formats. Z.A. was employed by GSK between October 2002 and November 2006 as a full-time employee, with a starting salary of £24,250 and an ending salary of £33,850. R.A.S. has received funding to attend international conferences from Boehringer Ingelheim and Talecris and for speaking at conferences organized by GSK and AstraZeneca; he served on advisory panels for Roche, GSK, and Merck Sharp & Dohme ($5,000 in 2006); he is in receipt of an unrestricted noncommercial grant from GSK (£30,000 in 2006) and Talecris (£317,000 in 2006). REFERENCES
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